Simulated bupivacaine pharmacokinetics after labor epidural analgesia followed by transversus abdominis plane block with liposomal bupivacaine for intrapartum cesarean delivery

To simulate bupivacaine pharmacokinetics in scenarios of labor epidural analgesia (LEA) extended for intrapartum cesarean delivery (CD) with epidural or intrathecal boluses, followed by transversus abdominis plane (TAP) block with liposomal bupivacaine (LB) for postcesarean analgesia. Bupivacaine plasma concentrations were simulated using a 2-compartment distribution model fit to previous study data. Virtual pharmacokinetic simulations. Virtual individuals (1000, each scenario) had uniform weight (80 kg) but varying absorption parameters. The 6 scenarios varied in LEA infusion duration (6 or 24 h), local anesthetic used for bolus to extend LEA (epidural lidocaine or intrathecal bupivacaine), TAP block regimen, and time between bolus and TAP block. Scenario outcomes included geometric mean (GM) peak bupivacaine plasma concentration (Cmax) with 95% prediction interval (PI), median (range) Cmax, and number of virtual individuals (per 1000) with Cmax reaching estimated toxicity thresholds (neurotoxicity: 2000 μg/L; cardiotoxicity: 4000 μg/L). In simulated scenarios of LEA infusion for 24 h with an epidural bolus of lidocaine 400 mg for CD followed 1 h later by TAP block, the GM Cmax for the scenarios with TAP blocks including either LB 266 mg plus bupivacaine hydrochloride 52 mg or bupivacaine hydrochloride 104 mg was 1860 (95% PI, 1107–3124) and 1851 (95% PI, 1085–3157) μg/L, respectively. Among 1000 virtual individuals for each scenario, 404 and 401 had Cmax reaching 2000 μg/L, respectively; 1 and 0 had Cmax reaching 4000 μg/L, respectively. For other scenarios, GM Cmax remained